In 1954, Gates reported the first total synthesis of morphine 1 by an ingenious yet simple route, utilizing a .beta.-dihydrothebainone-dihydrothebainone isomerization sequence in order to adjust the C.sub.14 stereocenter. Since Gates's original approach, a total of 16 syntheses have been reported. The majority (nine of them), including the most recent one of Overman, proceed via 1-benzylisoquinoline intermediates, with the crucial step being C.sub.12 -C.sub.13 bond formation. These syntheses are formalized by intercepting Gates's dihydrothebainone (or .beta.-dihydrothebainone) or by producing thebaine. The most efficient routes to date, those of Rice and Beyerman, have also used this strategy. Despite a number of attempts, only one successful synthesis (Evans) utilized a C.sub.10 -C.sub.11 closure late in the synthesis in order to complete the morphinan skeleton, followed by adjustment of stereochemistry at C.sub.14. ##STR3##
In 1994, Parker reported the full details of a radical cascade approach (published in a preliminary form in 1992)to racemic 1.